60 research outputs found
Determination of L-ascorbyl 6-palmitate in breadmaking using reverse-phase high-performance liquid chromatography (HPLC) with electrochemical (EC) detection
Call number: LD2668 .T4 1986 H86Master of ScienceGrain Science and Industr
The Interleukin-11/IL-11 receptor promotes glioblastoma survival and invasion under glucose-starved conditions through enhanced glutaminolysis
Glioblastoma cells adapt to changes in glucose availability through metabolic plasticity allowing for cell survival and continued progression in low-glucose concentrations. However, the regulatory cytokine networks that govern the ability to survive in glucose-starved conditions are not fully defined. In the present study, we define a critical role for the IL-11/IL-11
A Cross-Sectional Characterization of Insulin Resistance by Phenotype and Insulin Clamp in East Asian Americans with Type 1 and Type 2 Diabetes
Classic features of type 1 and type 2 diabetes may not apply in Asian Americans, due to shared absence of common HLA DR-DQ genotype, low prevalence of positive anti-islet antibodies and low BMI in both types of diabetes. Our objective was to characterize diabetic phenotypes in Asian Americans by clamp and clinical features.This was a cross-sectional study conducted in a referral center. Thirty East young Asian American adult volunteers (27.6±5.5 years) with type 1, type 2 diabetes or controls underwent hyperinsulinemic euglycemic clamp to assess insulin resistance and DEXA to assess adiposity.Gender, BMI, waist/hip ratio, leptin, LDL, anti-GAD, anti-IA2 antibodies and C-reactive protein were similar among three groups. Serum C-peptide, adiponectin, free fatty acid, HDL concentrations and truncal fat by DEXA, were different between diabetic groups. Glucose disposal rate by clamp was lowest in type 2 diabetes, followed by type 1 diabetes and controls (5.43±2.70, 7.62±2.59, 8.61±2.37 mg/min/kg, respectively, p = 0.001). Free fatty acid concentration universally plummeted during steady state of the clamp procedure regardless of diabetes types in all three groups. Adipocyte fatty acid binding protein in the entire cohort (r = -0.625, p = 0.04) and controls (r = -0.869, p = 0.046) correlated best with insulin resistance, independent of BMI.Type 2 diabetes in Asian Americans was associated with insulin resistance despite having low BMI as type 1 diabetes, suggesting a potential role for targeting insulin resistance apart from weight loss. Adipocyte fatty acid binding protein, strongly associated with insulin resistance, independent of adiposity in the young Asian American population, may potentially serve as a biomarker to identify at-risk individuals. Larger studies are needed to confirm this finding
Reduced cytochrome P4501A activity and recovery from oxidative stress during subchronic benzo[a]pyrene and benzo[e]pyrene treatment of rainbow trout
Author Posting. © The Author(s), 2011. This is the author's version of the work. It is posted here by permission of Elsevier B.V. for personal use, not for redistribution. The definitive version was published in Toxicology and Applied Pharmacology 254 (2011): 1-7, doi:10.1016/j.taap.2011.04.015.This
study
assessed
the
role
of
aryl
hydrocarbon
receptor
(AHR)
affinity,
and
cytochrome
P4501A
(CYP1A)
protein
and
activity
in
polyaromatic
hydrocarbon
(PAH)-‐induced
oxidative
stress.
In
the
1-‐100
nM
concentration
range
benzo[a]pyrene
(BaP)
but
not
benzo[e]pyrene
(BeP)
competitively
displaced
2
nM
[3H]2,
3,
7,
8-‐tetrachloro-‐dibenzo-‐p-‐dioxin
from
rainbow
trout
AHR2α.
Based
on
appearance
of
fluorescent
aromatic
compounds
in
bile
over
3,
7,
14,
28
or
50
days
of
feeding
3
μg
of
BaP
or
BeP/g
fish/day,
rainbow
trout
liver
readily
excreted
these
polyaromatic
hydrocarbons
(PAHs)
and
their
metabolites
at
near
steady
state
rates.
CYP1A
proteins
catalyzed
more
than
98%
of
ethoxyresorufin-‐O-‐deethylase
(EROD)
activity
in
rainbow
trout
hepatic
microsomes.
EROD
activity
of
hepatic
microsomes
initially
increased
and
then
decreased
to
control
activities
after
50
days
of
feeding
both
PAHs.
Immunohistochemistry
of
liver
confirmed
CYP1A
protein
increased
in
fish
fed
both
PAHs
after
3
days
and
remained
elevated
for
up
to
28
days.
Neither
BaP
nor
BeP
increased
hepatic
DNA
adduct
concentrations
at
any
time
up
to
50
days
of
feeding
these
PAHs.
Comet
assays
of
blood
cells
demonstrated
marked
DNA
damage
after
14
days
of
feeding
both
PAHs
that
was
not
significant
after
50
days.
There
was
a
strong
positive
correlation
between
hepatic
EROD
activity
and
DNA
damage
in
blood
cells
over
time
for
both
PAHs.
Neither
CYP1A
protein
nor
3-‐
nitrotyrosine
(a
biomarker
for
oxidative
stress)
immunostaining
in
trunk
kidney
were
significantly
altered
by
BaP
or
BeP
after
3,
7,
14,
or
28
days.
There
was
no
clear
association
between
AHR2α
affinity
and
BaP
and
BeP-‐induced
oxidative
stress.The
Oregon
Agricultural
Experiment
Station,
Northwest
Fisheries
Science
Center,
and
RO1ES006272
from
the
National
Institute
of
Health
supported
this
work
Needle syringe programmes and opioid substitution therapy for preventing HCV transmission among people who inject drugs: findings from a Cochrane Review and meta-analysis.
AIMS: To estimate the effects of needle syringe programmes (NSP) and opioid substitution therapy (OST), alone or in combination, for preventing acquisition of Hepatitis C virus (HCV) in people who inject drugs (PWID). METHODS: Systematic review and meta-analysis. Bibliographic databases were searched for studies measuring concurrent exposure to current OST (within last 6 months) and/or NSP and HCV incidence among PWID. High NSP coverage was defined as regular NSP attendance or ≥100% coverage (receiving sufficient or greater number of needles/syringes per reported injecting frequency). Studies were assessed using the Cochrane risk of bias in non-randomised studies tool. Random effects models were used in meta-analysis. RESULTS: We identified 28 studies (n=6279) in North America (13), UK (5), Europe (4), Australia (5), and China (1). Studies were at moderate (2), serious (17) critical (7) and non-assessable risk of bias (2). Current OST is associated with 50% (risk ratio (RR) 0.50 95% CI 0.40-0.63) reduction in HCV acquisition risk, consistent across region and with low heterogeneity (I(2) =0, p=0.889). Weaker evidence was found for high NSP coverage (RR=0.79 95% CI 0.39-1.61) with high heterogeneity (I(2) =77%, p=0.002). After stratifying by region, high NSP coverage in Europe was associated with a 56% reduction in HCV acquisition risk (RR=0.44, 95% CI 0.24-0.80) with low heterogeneity (I(2) =12.3%, p=0.337) but not in North America (RR=1.58, I(2) =89.5%, p=<0.001). Combined OST/NSP is associated with a 76% reduction in HCV acquisition risk (RR=0.24 95% CI=0.07-0.89, I(2) =80% p=0.007). According to GRADE criteria, the evidence on OST and combined OST/NSP is low quality while NSP is very low. CONCLUSIONS: Opioid substitution therapy reduces risk of hepatitis C acquisition and is strengthened in combination with needle syringe programmes. There is weaker evidence for the impact of needle syringe programmes alone, although stronger evidence that high coverage is associated with reduced risk in Europe
Needle syringe programmes and opioid substitution therapy for preventing hepatitis C transmission in people who inject drugs.
BACKGROUND: Needle syringe programmes and opioid substitution therapy for preventing hepatitis C transmission in people who inject drugsNeedle syringe programmes (NSP) and opioid substitution therapy (OST) are the primary interventions to reduce hepatitis C (HCV) transmission in people who inject drugs. There is good evidence for the effectiveness of NSP and OST in reducing injecting risk behaviour and increasing evidence for the effectiveness of OST and NSP in reducing HIV acquisition risk, but the evidence on the effectiveness of NSP and OST for preventing HCV acquisition is weak. OBJECTIVES: To assess the effects of needle syringe programmes and opioid substitution therapy, alone or in combination, for preventing acquisition of HCV in people who inject drugs. SEARCH METHODS: We searched the Cochrane Drug and Alcohol Register, CENTRAL, the Cochrane Database of Systematic Reviews (CDSR), the Database of Abstracts of Reviews of Effects (DARE), the Health Technology Assessment Database (HTA), the NHS Economic Evaluation Database (NHSEED), MEDLINE, Embase, PsycINFO, Global Health, CINAHL, and the Web of Science up to 16 November 2015. We updated this search in March 2017, but we have not incorporated these results into the review yet. Where observational studies did not report any outcome measure, we asked authors to provide unpublished data. We searched publications of key international agencies and conference abstracts. We reviewed reference lists of all included articles and topic-related systematic reviews for eligible papers. SELECTION CRITERIA: We included prospective and retrospective cohort studies, cross-sectional surveys, case-control studies and randomised controlled trials that measured exposure to NSP and/or OST against no intervention or a reduced exposure and reported HCV incidence as an outcome in people who inject drugs. We defined interventions as current OST (within previous 6 months), lifetime use of OST and high NSP coverage (regular attendance at an NSP or all injections covered by a new needle/syringe) or low NSP coverage (irregular attendance at an NSP or less than 100% of injections covered by a new needle/syringe) compared with no intervention or reduced exposure. DATA COLLECTION AND ANALYSIS: We followed the standard Cochrane methodological procedures incorporating new methods for classifying risk of bias for observational studies. We described study methods against the following 'Risk of bias' domains: confounding, selection bias, measurement of interventions, departures from intervention, missing data, measurement of outcomes, selection of reported results; and we assigned a judgment (low, moderate, serious, critical, unclear) for each criterion. MAIN RESULTS: We identified 28 studies (21 published, 7 unpublished): 13 from North America, 5 from the UK, 4 from continental Europe, 5 from Australia and 1 from China, comprising 1817 incident HCV infections and 8806.95 person-years of follow-up. HCV incidence ranged from 0.09 cases to 42 cases per 100 person-years across the studies. We judged only two studies to be at moderate overall risk of bias, while 17 were at serious risk and 7 were at critical risk; for two unpublished datasets there was insufficient information to assess bias. As none of the intervention effects were generated from RCT evidence, we typically categorised quality as low. We found evidence that current OST reduces the risk of HCV acquisition by 50% (risk ratio (RR) 0.50, 95% confidence interval (CI) 0.40 to 0.63, I(2) = 0%, 12 studies across all regions, N = 6361), but the quality of the evidence was low. The intervention effect remained significant in sensitivity analyses that excluded unpublished datasets and papers judged to be at critical risk of bias. We found evidence of differential impact by proportion of female participants in the sample, but not geographical region of study, the main drug used, or history of homelessness or imprisonment among study samples.Overall, we found very low-quality evidence that high NSP coverage did not reduce risk of HCV acquisition (RR 0.79, 95% CI 0.39 to 1.61) with high heterogeneity (I(2) = 77%) based on five studies from North America and Europe involving 3530 participants. After stratification by region, high NSP coverage in Europe was associated with a 76% reduction in HCV acquisition risk (RR 0.24, 95% CI 0.09 to 0.62) with less heterogeneity (I(2) =0%). We found low-quality evidence of the impact of combined high coverage of NSP and OST, from three studies involving 3241 participants, resulting in a 74% reduction in the risk of HCV acquisition (RR 0.26 95% CI 0.07 to 0.89). AUTHORS' CONCLUSIONS: OST is associated with a reduction in the risk of HCV acquisition, which is strengthened in studies that assess the combination of OST and NSP. There was greater heterogeneity between studies and weaker evidence for the impact of NSP on HCV acquisition. High NSP coverage was associated with a reduction in the risk of HCV acquisition in studies in Europe
Erratum to: Methods for evaluating medical tests and biomarkers
[This corrects the article DOI: 10.1186/s41512-016-0001-y.]
New genetic loci link adipose and insulin biology to body fat distribution.
Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms
AI is a viable alternative to high throughput screening: a 318-target study
: High throughput screening (HTS) is routinely used to identify bioactive small molecules. This requires physical compounds, which limits coverage of accessible chemical space. Computational approaches combined with vast on-demand chemical libraries can access far greater chemical space, provided that the predictive accuracy is sufficient to identify useful molecules. Through the largest and most diverse virtual HTS campaign reported to date, comprising 318 individual projects, we demonstrate that our AtomNet® convolutional neural network successfully finds novel hits across every major therapeutic area and protein class. We address historical limitations of computational screening by demonstrating success for target proteins without known binders, high-quality X-ray crystal structures, or manual cherry-picking of compounds. We show that the molecules selected by the AtomNet® model are novel drug-like scaffolds rather than minor modifications to known bioactive compounds. Our empirical results suggest that computational methods can substantially replace HTS as the first step of small-molecule drug discovery
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